Aortic valve repair

ABSTRACT

The present invention provides devices and methods for decalcifying an aortic valve. The methods and devices of the present invention break up or obliterate calcific deposits in and around the aortic valve through application or removal of heat energy from the calcific deposits.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit and priority of U.S.Provisional Application Ser. No. 60/635,275, filed Dec. 9, 2004; U.S.Provisional Application Ser. No. 60/662,764, filed Mar. 16, 2005; andU.S. Provisional Application Ser. No. 60/698,297, filed on Jul. 11,2005; the complete disclosures of which are expressly incorporatedherein by reference.

BACKGROUND OF THE INVENTION

Aortic valve stenosis is a common cardiac disease resulting inapproximately 65,000 aortic valve replacement surgeries in the UnitedStates annually. Aortic valve stenosis can occur via several etiologiesincluding rheumatic disease, congenital and degenerative calcificstenosis. In developing countries, rheumatic fever results in thickeningand progressive immobility of the valve tissues. Calcific diseaseaccounts for almost all of the cases of aortic stenosis in the UnitedStates and in developed nations where rheumatic disease is rare.

Over time, a build up of calcium can occur in the annulus of the valve,along the leaflet cusps and on or within the leaflets. This calcificmaterial such as nodular calcific deposits may be superimposed on anunderlying fibrotic aortic valve leaflet or calcific deposits may bediffusely distributed throughout the body (spongiosa) of the aorticvalve leaflets. Although distribution and type of deposits may differdepending on valve geometry (bicuspid, tricuspid), the depositsgenerally contribute to leaflet immobility, thickening and otherpathologies that lead to degenerative valve function. The presence andprogression of this disease leads to a decreased functional area of thevalve and dramatically reduced cardiac output.

In the late 1980s and early 1990s balloon dilation of the aortic valve,or valvuloplasty, became a popular therapy for aortic valve stenosis.Dilation of the aortic valve using large angioplasty balloons fromeither an antegrade (transeptal) or retrograde (aortic) approachresulted in improvements in left ventricular ejection fractions(increased cardiac output), decreases in pressure gradients across thevalve, and increases in valve cross-sectional area. Variousvalvuloplasty balloon designs and other approaches, including energybased therapies, have been disclosed in U.S. Pat. No. 3,667,474 Lapkin,U.S. Pat. No. 4,484,579 Meno, U.S. Pat. No. 4,787,388 Hoffman, U.S. Pat.No. 4,777,951 Cribier, U.S. Pat. No. 4,878,495 and U.S. Pat. No.4,796,629 to Grayzel, U.S. Pat. No. 4,819,751 Shimada, U.S. Pat. No.4,986,830 Owens, U.S. Pat. No. 5,443,446 and U.S. Pat. No. 5,295,958 toSchturman, U.S. Pat. No. 5,904,679 Clayman, U.S. Pat. No. 5,352,199 andU.S. Pat. No. 6,746,463 to Tower, the disclosures of which are expresslyincorporated herein by reference.

In addition, various surgical approaches to de-calcify the valve lesionswere attempted utilizing ultrasonic devices to debride or obliterate thecalcific material. Such devices include the CUSA Excel™ UltrasonicSurgical Aspirator and handpieces (23 kHz and 36 kHz, Radionics, TYCOHealthcare, Mansfield, Mass.). Further work, approaches and results havebeen documented in “Contrasting Histoarchitecture of calcified leafletsfrom stenotic bicuspid versus stenotic tricuspid aortic valves,” Journalof American College of Cardiology 1990 April; 15(5):1104-8, UltrasonicAortic Valve Decalcification: Serial Doppler Echocardiographic FollowUp” Journal of American College of Cardiology 1990 September; 16(3):623-30, and “Percutaneous Balloon Aortic Valvuloplasty: AntegradeTransseptal vs. Conventional Retrograde Transarterial Approach”Catheterization and Cardiovascular interventions 64:314-321 (2005), thedisclosures of which are expressly incorporated by reference herein.

Devices and techniques have suffered from only a modest ability toincrease valve cross-sectional area, however. For instance, many studiesshowed that a pre-dilatation area of about 0.6 cm² could be opened toonly between about 0.9 to about 1.0 cm². It would be desirable to opensuch a stenosis to an area closer to about 1.2 to about 1.5 cm². Inaddition to opening the cross-sectional area, it may be desirable totreat the leaflets and surrounding annulus to remove calcific depositsthat stiffen the valve, impair flow dynamics, and otherwise degeneratevalve function. Toward this end, other techniques such as directsurgical ultrasonic debridement of calcium deposits have had somesuccess, but required an open surgical incision, thereby increasing therisk to the patient.

Although balloon dilatation offered patients a viable, less invasivealternative, it fell into disfavor in the early to mid 1990s primarilyas a result of rapid restenosis of the valve post treatment. At sixmonths, reports of restenosis rates were commonly in excess of 70-80%.Today, balloon valvuloplasty is primarily reserved for palliative carein elderly patients who are not candidates for surgical replacement dueto comorbid conditions.

Recent clinical focus on technologies to place percutaneous valvereplacement technologies have also caused some to revisit valvuloplastyand aortic valve repair. Corazon, Inc. is developing a system whichisolates the leaflets of the aortic valve so that blood flow through thecenter of the device is preserved while calcium dissolving or softeningagents are circulated over and around the leaflets. See for example,United States Patent Application Publication 2004/0082910, thedisclosure of which is expressly incorporated herein by reference. Thehope is that reducing the stiffness of the leaflets by softening thecalcium will allow for more normal functioning of the valve andincreased cardiac output. The system is complex, requires upwards of 30minutes of softening agent exposure time, and has resulted in completeAV block and emergency pacemaker implantation in some patients.

In addition, other technologies have been documented to address aorticstenosis in various ways. U.S. Patent Application Publication2005/007219 to Pederson discloses balloon materials and designs, as wellas ring implants for use in valvuloplasty and treatment of aorticstenosis, the disclosure of which is expressly incorporated herein byreference. Further, Dr. Pederson recently presented initial results ofthe RADAR study for aortic valve stenosis therapy. This study combinestraditional balloon valvuloplasty with external beam radiation to try toprevent the restenosis which occurs post-dilatation. While radiationtherapy has been shown to have a positive impact on restenosis incoronary angioplasty, the methods employed in the RADAR study requirethat the patient undergo a minimum of 4-6 separate procedures, theinitial valvuloplasty plus 3-5 separate radiation therapy sessions.These radiation therapy sessions are similar to those used for radiationtreatment for cancer.

Over the past three years, dramatic advances in the prevention ofrestenosis after coronary balloon angioplasty and stenting have beenmade by the introduction of drug-eluting stents by companies like BostonScientific and Johnson & Johnson. These devices deliver a controlled andprolonged dose of antiproliferative agents to the wall of the coronaryartery in order to manage the sub-acute wound healing and prevent thelong-term hyperproliferative healing response that caused restenosis inbare metal stents or in stand-alone angioplasty. Furthermore, variousadvances have been made on the administration of anti-calcificationdrugs, including ACE inhibitors, statins, and angiotensins, specificallyangiotensin II, as detailed in United States Patent ApplicationPublication 2004/0057955, the disclosure of which is expresslyincorporated herein by reference.

While the conventional methods have proven to be reasonably successful,the problem of aortic valve stenosis and subsequent restenosis aftervalvuloplasty or other intervention still requires better solutions. Thepresent invention provides various devices and methods that create moreeffective treatments for aortic stenosis and prevent or reduce theincidence and/or severity of aortic restenosis. In addition, the presentinventions provides methods and devices for decalcification ordebridement of aortic stenosis, either as a stand alone therapy or inconjunction with conventional techniques, such as traditionalvalvuloplasty, stenting, valve repair, and percutaneous or surgicalvalve replacement.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to the repair of aortic and other cardiacvalves, and more particularly devices and methods for calcium removaland anti-restenosis systems for achieving such repair. The invention cantake a number of different forms, including apparatus, acuteinterventions performed at the time of the aortic repair orvalvuloplasty, or temporary or permanent implant, and the like.

In one aspect, the methods and devices of the reduce or removecalcifications on or around the valve through application or removal ofenergy to disrupt the calcifications. The present invention may applyultrasound energy, RF energy, a mechanical energy, or the like, to thevalve to remove the calcification from the valve. Alternatively, it maybe desirable to instead remove energy (e.g. cryogenically cooling) fromthe calcification to enhance the removal of the calcification from thevalve. In all cases, it will be desirable to create an emboliccontainment region over a localized calcific site on or near the cardiacvalve. Such containment may be achieved by creating a structure aboutthe localized site and/or by actively aspirating embolic particles fromthe site as they are created. Suitable structures include filters,baskets, balloons, housings and the like.

In another aspect of the present invention, treatment catheters areprovided to deliver a working element to the vicinity of the diseasedvalve. Working element can include an ultrasonic element, or any otherdelivery mechanism or element that is capable of disrupting, e.g.,breaking up or obliterating calcific deposits in and around the cardiacvalve. Such devices may be steerable or otherwise positionable to allowthe user to direct the distal end of the catheter grossly for initialplacement through the patient's arteries to the valve, and thenprecisely adjust placement prior to and/or during treatment.

In another aspect, the present invention provides a treatment catheterthat comprises a mechanical element that can disrupt, e.g., mechanicallybreak up, obliterate, and remove the calcific deposits in and around theaortic valve. Similar to the ultrasonic-based catheters, the cathetercomprising the mechanical element may be steerable or otherwisearticulable to allow the user to direct the distal end of the cathetergrossly for initial placement, and then fine tune placement duringtreatment.

In a further aspect of the present invention, systems including a guidecatheter may also be employed to position the treatment catheter at thesite of the disease to be treated, either as a separate catheter or aspart of the treatment device. In one embodiment, a main guide cathetermay be used to center a secondary positioning catheter that contains thetreatment catheter over the aortic valve. The treatment catheter maythen be further articulated to provide even further directionality tothe working end. Various other apparatus and methods may be employed forpositioning and stabilizing the treatment catheter, including shapedballoons, baskets or filters and methods of pacing the heart.

In a further aspect of the present invention, methods may be used todisrupt the calcified sites and trap and evacuate emboli and otherdebris from the treatment site, using filters located on the treatmentcatheter, suction housings located on the treatment catheter, perfusionballoons linked with aspiration devices, separate suction catheters,separate filter devices either at the treatment site or downstream fromthe treatment site, and/or external filter and perfusion systems.Certain filter embodiments may be shaped to allow the treatment catheterto access the location to be treated, while still allowing flow throughthe valve (e.g. treating one leaflet at a time).

In particular, methods for treating cardiac valves according to thepresent invention comprise creating an emboli containment region over acalcific site and delivering energy (including cryotherapy) to disruptsaid site and potentially create emboli which are contained in thecontainment region. The containment regions will typically be localizeddirectly over a target site, usually having a limited size so that theassociated aorta or other blood vessel is not blocked or occluded. Thecontainment region may be created using a barrier, such as a filterstructure, basket, or balloon over the calcified site. Alternatively oradditionally, the containment region may be created by localizedaspiration to remove substantially all emboli as they are formed. Theenergy applied may be ultrasound, radiofrequency, microwave, mechanical,cryogenic, or any other type of energy capable of disrupting valvecalcifications.

In a further aspect of the present invention, the methods may virtuallydisintegrate the calcification through the use a media that containsmicrospheres or microbubbles, such as Optison™ sold by GE Healthcare(www.amershamhealth-us.com/optison/). Delivery of an ultrasound energy(or other form of energy, for example, laser, RF, thermal, energy) tothe media may cause the microspheres to rupture, which causes a releaseof energy toward the valve, which may help remove the calcificationaround and on the valve. Bioeffects Caused by Changes in AcousticCavitation Bubble Density and Cell Concentration: A Unified ExplanationBased on Cell-to-Bubble Ratio and Blast Radius, Guzman, et al.Ultrasound in Med. & Biol., Vol. 29, No. 8, pp. 1211-1222 (2003).

Certain imaging and other monitoring modalities may be employed priorto, during or after the procedure of the present invention, utilizing avariety of techniques, such as intracardiac echocardiography (ICE),transesophageal echocardiography (TEE), fluoroscopy, intravascularultrasound, angioscopy or systems which use infrared technology to “seethrough blood”, such as that under development by Cardio-Optics, Inc.

Various energy sources may be utilized to effect the treatment of thepresent invention, including RF, ultrasonic energy in varioustherapeutic ranges, and mechanical (non-ultrasound) energy. The distaltips of the RF, ultrasonic treatment catheters, and mechanical treatmentcatheters of the present invention may have a variety of distal tipconfigurations, and be may be used in a variety of treatment patterns,and to target specific locations within the valve.

In addition, intravascular implants are contemplated by the presentinvention, including those placed within the valve annulus, supraannular, sub annular, or a combination thereof to assist in maintaininga functional valve orifice. Such implants may incorporate variouspharmacological agents to increase efficacy by reducing restenosis, andotherwise aiding valve function. Implants may be formed of variousmetals, biodegradable materials, or combinations thereof.

These devices may all be introduced via either the retrograde approach,from the femoral artery, into the aorta and across the valve from theascending aorta, or through the antegrade approach—transeptal, acrossthe mitral valve, through the left ventricle and across the aorticvalve.

In other aspects, the present invention provides an anti-restenosissystem for aortic valve repair. Acute interventions are performed at thetime of the aortic repair or valvuloplasty and may take the form of atemporary or permanent implant.

These implant devices may all be introduced via either the retrogradeapproach, from the femoral artery, into the aorta and across the valvefrom the ascending aorta, or through the antegradeapproach—trans-septal, across the mitral valve, through the leftventricle and across the aortic valve, and will provide for delivery ofanti-restenosis agents or energy to inhibit and/or repair valverestenosis.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a suction catheter constructed in accordance with theprinciples of the present invention.

FIG. 2 is a cross-sectional view of the catheter of FIG. 1.

FIGS. 3 and 4 are detailed views of the distal end of the catheter ofFIG. 1, with FIG. 4 showing a suction housing in an expandedconfiguration.

FIG. 5 is similar to FIG. 4, showing the catheter without a guidewire.

FIGS. 6-8 show modified suction housings.

FIGS. 9 and 10 show suction housings having different depths.

FIGS. 11-13 show suction housings having rigid or semi-rigid membersaround their circumferences.

FIG. 14 shows a suction catheter having a stabilizing structure near itsdistal end.

FIG. 15 illustrates how a guiding catheter would be used to place thecatheters of the present invention above a treatment area.

FIGS. 16 and 17 show how suction catheters would be placed through theguide catheters.

FIGS. 18-22 illustrate the use of treatment catheters having ultrasonicprobes for decalcifying leaflets in accordance with the principles ofthe present invention.

FIG. 23 illustrates a catheter having a distal portion shaped tocorrespond to a shape of a targeted valve leaflet.

FIG. 24 illustrates a catheter having a distal end with an annulartreatment surface adapted to apply energy to a valve annulus.

FIGS. 25A-25D illustrate catheters having different working ends inaccordance with the principles of the present invention.

FIGS. 26-28 illustrate catheters having ultrasonic transmission membersand enlarged working ends.

FIGS. 29-31 illustrate catheters having enlarged distal working endswith central lumens therethrough.

FIGS. 32 and 33 illustrate catheters having ultrasonic transmissionelements adjacent a working end.

FIGS. 34-37 illustrate different patterns of motion which may beimparted by the electronic catheters of the present invention.

FIG. 38 illustrates a catheter having a force limiting feature.

FIGS. 39 and 40 illustrate a catheter having a deflectable distal end.

FIGS. 41 and 42 illustrate treatment catheters being advanced through asheath.

FIG. 43 illustrates an ultrasonic catheter having a distal horn and aPZT stack.

FIG. 44 illustrates a suction housing placed over a PZT stack andultrasonic horn in an embodiment of the present invention.

FIG. 45 illustrates a proximal housing for steering a distal end of thecatheters of the present invention.

FIG. 46 illustrates use of a pair of suction catheters for treating avalve in accordance with the principles of the present invention.

FIG. 47 illustrates a catheter having an eccentrically loaded coil inthe working end thereof.

FIGS. 48 and 49 show variations on the coil of FIG. 47.

FIGS. 50-52 illustrate catheters having mechanical elements in theirdistal ends.

FIGS. 53 and 54 show catheters having distal impellers and grinders.

FIGS. 55-57 illustrate catheters having disk-like grinders with abrasivesurfaces.

FIGS. 58 and 59 illustrate rotating burrs which may be placed in thedistal end of the catheters of the present invention.

FIG. 60 illustrates a catheter having a piezoelectric film element inits distal end.

FIGS. 61 and 62 show guiding catheters having filter elements at theirdistal ends which are used for introducing the catheters of the presentinvention.

FIG. 63 illustrates a filter device deployed to protect an entire regionof treatment.

FIG. 64 illustrates a filter device covering a single leaflet.

FIG. 65 shows a filter shape optimized for a leaflet at the treatmentsite.

FIGS. 66-68 show catheter positions optimized for reducing calciumdeposits.

FIG. 69 shows a device having an open lattice structure.

FIGS. 70-72 show implants formed from lattice wire structures.

FIGS. 73-76 illustrate implants having multiple loops.

FIGS. 77-80 show embodiments of the present invention for deliveringdrugs to the target treatment sites.

FIGS. 81 and 82 illustrate catheters having balloons with both drugrelease capability and blood perfusion capability.

FIGS. 83 and 84 show implantable devices having deployable struts.

FIGS. 85 and 86 show implantable devices having anchoring elements whichlie against the wall of the aorta.

FIGS. 87-89 show embodiments where the device struts also provide foranchoring.

DETAILED DESCRIPTION OF THE INVENTION

Treatment Catheter Design—General

Treatment catheters 10 (FIG. 1) of the present invention typicallycomprise an elongate catheter body 12 that comprises a proximal end 14,a distal end 16, and one or more lumens 18, 20 (FIG. 2) within thecatheter body. The distal end 16 may optionally comprise a suctionhousing 22 (FIGS. 4 and 5) that extends distally from the distal end ofthe catheter body 12 for isolating the leaflet during treatment as wellas providing a debris evacuation path during treatment and protectingthe vasculature from adverse embolic events. An energy transmissionelement 24 (e.g., a drive shaft, wire leads, or a waveguide-ultrasonictransmission element, or the like) may be positioned in one of thelumens in the elongate body 12 and will typically extend from theproximal end to the distal end of the catheter body. A handle 26 iscoupled to the proximal end 14 of the elongate catheter body 12. Agenerator (e.g., RF generator, ultrasound generator, motor, opticalenergy source, etc.) may be coupled to the handle to deliver energy to adistal waking end 28, the energy transmission element 24 that isdisposed within a lumen of the catheter body. As described herein, thedistal working element 28 may be coupled to the distal end of the energytransmission element 24 to facilitate delivery of the energy to thecalcification on the aortic valve.

Typically, the treatment catheters 10 of the present invention areconfigured to be introduced to the target area “over the wire.” Thetreatment catheters may be positioned adjacent the aortic valve througha guide catheter or sheath. As such, the treatment catheters of thepresent invention may comprise a central guidewire lumen 20 forreceiving a guidewire GW (FIG. 2). The guidewire lumen 20 of thetreatment catheters of the present invention may also be used forirrigating or aspirating the target area. For example, while not shown,the handle may comprise one or more ports so as to allow for irrigationof the target leaflet and/or aspiration of the target area. Anirrigation source and/or an aspiration source may be coupled to theport(s), and the target area may be aspirated through one of the lumenof the catheter and/or irrigated through one of the lumens of thecatheter. In one embodiment, one of the irrigation source and aspirationsource may be coupled to the central guidewire lumen (central lumen) andthe other of the aspiration source and the irrigation source may becoupled to the lumen that is coaxial to the guidewire lumen. In someembodiments, however, there will be no inner guidewire lumen and theguidewire will simply extend through the ultrasound waveguide and therotatable drive shaft, as shown in FIGS. 3, 4 and 6.

As noted above, the treatment catheters 10 of the present invention maycomprise a suction housing positioned at the distal end of the catheterbody having an expanded configuration and a retracted configuration andconfigured to conform to the valve leaflet to be treated. While thesuction housing 22 may be fixedly attached at the distal end, inpreferred embodiments, the suction housing is movable between aretracted configuration (FIG. 3) and an expanded configuration (FIGS. 4and 5). A separate sheath may also be retracted to expose the suctionhousing and advanced to fold the housing. The suction housing may bemade from silicone or urethane and may be reinforced with an internalframe or mesh reinforcement to provide structural support or to enhanceplacement of the housing on a specified area of the valve leaflet. Thehousing may further act as an embolic filter as detailed later in thisspecification.

In the embodiment of FIG. 4, the energy transmission element 24 isadvanced beyond the distal end of the catheter body 12 and into thesuction housing 22. The guidewire GW is positioned through an opening inthe distal tip. As in FIG. 5, once the treatment catheter is positionedat the target area, the guidewire GW is withdrawn and the distal workingelement 28 is ready for use to treat the calcification.

In FIG. 6, the suction housing 22 is shaped to substantially conform tothe shape of a bicuspid valve leaflet. By shaping the suction housing toconform to the shape of the leaflet, the suction housing may be betterconfigured to isolate the target leaflet. In other embodiments, thesuction housing may be shaped to substantially conform to a tricuspidvalve (FIGS. 7 and 8), etc.

The depth of the suction housing may take many forms such that it iscompatible with the valve to be treated. For example, the suctionhousing 22 may be shallow (FIG. 9) or deep (FIG. 10). The depth on thecup can reduce or eliminate obstructing the coronary ostia if one of theleaflets under treatment is a coronary leaflet.

The suction cups/housings may also have rigid or semi-rigid membersaround the circumference or part of the circumference of the housing topreferentially align the cup on certain valve features, such as theannulus. The suction cup housings have a depth range of 0.1″ to 0.5″ anda diameter of 15 mm to 30 mm. The cup or housing may have fingers 30 orlongitudinal stabilizing elements 32 to assist in placing the housingagainst the valve as shown in FIGS. 11, 12, and 13.

Such stabilizing elements may also be in the form of pleats, rings orhemispherical elements, or other reinforcements to assist the device toseat within the annulus of the valve or against the leaflet. Suchreinforcements or stabilizing elements may be formed of stainless steel,NiTi (superelastic or shape memory treated), Elgiloy®, cobalt chromium,various polymers, or may be in the form of an inflatable ringed cup. Thecup or housing of the present invention is intended to function toprovide sufficient approximation with the treatment area so as tostabilize or localize the working element while also minimizing embolicevents. It that sense, it is substantially sealing against the treatmentregion, but such seal is not necessarily an “airtight” seal, but anapproximation that performs the desired functions listed above.

In addition, certain stabilizing devices 36, 38 may be located on themain catheter shaft 12 to provide stability within the aorta, and may,in some cases, extend through the valve leaflets L below the valve tofurther stabilize the treatment device, as shown in FIG. 14.

Given the variety of leaflet geometries (e.g. size, curvature) fromleaflet to leaflet, and patient to patient, it may be desirable toprovide a main treatment catheter through which a variety of sized andshaped cups or housings can be passed, depending on the particulargeometry to be treated. For example, a system could include a main guidecatheter GC placed over the treatment area as depicted in FIG. 15: Thetreatment area (leaflets) include the coronary leaflet (CL), thenon-coronary leaflet (NCL) and the non-coronary leaflet (center) (NCLC).As shown below in FIG. 16, once the guide catheter GC is in place afirst treatment catheter 40 having a distal housing 42 adapted toconform to the NCL is advanced as indicated by arrow S1. The leaflet istreated and the NCL housing catheter is withdrawn as indicated by S2.The guide catheter position is then adjusted as indicated by arrow S3 tobetter approximate the CL. CL housing catheter is the advanced throughthe guide as indicated by arrow S4. Once the CL position is treated, theCL housing catheter is removed as indicated by arrow S5. As furtherdepicted in FIG. 17, the guide catheter GC is then repositioned to treatNCLC as indicated by arrow S6, and finally the NCLC housing catheter isadvanced through the guide according to arrow S7. Once the treatment iscomplete, the NCLC is removed as indicated by arrow S8 and the guide isremoved and procedure completed.

It is within the scope of the present invention to use any one of thesesteps, in any order to treat the targeted region, for example, oneleaflet may be treated only, more than one leaflet, and in any orderaccording to the type of calcification, health of the patient, geometryof the target region or preference of the operator.

Ultrasound Treatment Catheters

In accordance with one aspect of the present invention a treatmentcatheter 50 is provided having an ultrasonic probe for decalcifying theleaflet. An ultrasonic probe 52 may be surrounded by a frame or sheath54. Both the frame and the sheath may be connected to a source ofultrasonic vibration (not shown). In certain embodiments, the probe 52is surrounded by a sheath or housing that enables the system to besubstantially sealed against the treatment surface via a source ofsuction attached at the proximal end of the catheter system andconnected to the catheter housing via a suction lumen in the catheterbody. Alternatively, the system may be placed or localized at thetreatment site with a mechanical clip or interface that physicallyattaches the housing to the treatment area (annulus or leaflet). Inoperation, the ultrasonic probe 52 is activated to disintegrate thecalcium on the leaflets, creating debris that may then be removedthrough a suction lumen in the catheter body 50. In some cases it may bedesirable to also infuse saline or other fluids into the housing areasimultaneously or prior to application of suction. It may beadvantageous to provide a cooling fluid to the ultrasonic waveguide aswell and to other embodiments such as one with a PZT stack at the distalend of the device. It may also be advantageous to infuseanti-calcification therapy to the site of the valve, including a ferricand/or stannic salt, or other solution as in known in the art to tan orotherwise make the leaflets resistant to calcium buildup, such as thetype set forth in U.S. Pat. No. 5,782,931, the contents of which isexpressly incorporated by reference herein. Another embodiment of anultrasonic probe 60 having a silicone cup is shown in FIG. 19 whereinfusate is indicated by arrows 62 and aspirate is indicated by arrows64.

In embodiments where a filter device 74 is disposed on the main cathetershaft (shown in FIG. 20), the ultrasonic probe 70 may be a separateelement, allowing the ultrasonic treatment catheter 72 to moveindependently within the sealed region. The treatment probe 70 may beoperated in a variety of directions and patterns that are furtherdetailed in the specification, including sweeping in a circular patternalong the cusp of each leaflet and creating concentric circles duringtreatment to effectively treat the entire leaflet, if necessary. In theabsence of a filter device, the ultrasonic element may be coaxial withthe suction housing and adapted to move independently therewithin.

As shown in FIG. 21, in accordance with another aspect of the presentinvention, a treatment catheter 80 may be placed through a series ofguide catheters 82, 84 to assist placement accuracy. The first guidemember 84 may be placed and anchored in the aortic root using either theshape of the guide to anchor against the aortic wall, or a separateballoon or filter device to stabilize the guide or a stabilizing ringmade from shape memory material or other suitable material that canprovide stabilization to allow the catheter to be directed to thetreatment site. A second steerable or articulable catheter 82 may thenbe placed through the initial guide to direct the treatment catheter toone area of the leaflet or other. The treatment catheter 80 may then beplaced through the system once these guides are in place, and deployeddirectly to the targeted valve region. In the case of a method thattreats one leaflet at a time, the steerable guide may then be actuatedto target the next treatment location, thereby directing the treatmentcatheter (and related filtering devices) to the next site. It may onlybe necessary to place one guide catheter prior to the treatmentcatheter, or alternatively, the treatment catheter may be steerable,allowing it to be placed directly to the treatment site without the aidof other guide catheters. The guide catheter may also be steerable andan integral part of the treatment catheter. Steerable guides such asthose depicted in US Patent Publications 2004/0092962 and 2004/0044350are examples, the contents of which is expressly incorporated byreference in its entirety. Treatment device may then re-directed to asecond treatment site, as shown in FIG. 22.

The distal portion 90 of the treatment catheters of the presentinvention may be shaped to substantially correspond to a shape of thetargeted leaflet L (e.g., formed to fit within shape of the leafletcusp, with the mouth of the housing being shaped to conform to theleaflet shape as shown in FIG. 23). This also enables the surface of theleaflet to be stabilized for treatment. The distal portion may have aninternal frame that supports the distal section during deployment andtreatment but is flexible such that it collapses into the treatmentcatheter or sheath to assist with withdrawal.

Alternatively, the treatment catheter 100 of the present invention maybe formed having a circumferential, annular treatment 102 surface toapply energy/vibration to the annulus to be treated. In this embodimentthe catheter may be placed antegrade or retrograde, or twocircumferential treatment surfaces may be used in conjunction with eachother, as shown in FIG. 24.

Various ultrasonic working ends may be used, depending on the type andlocation of the disease to be treated. For example, the distal tip of anultrasonic catheter may be coupled to a ultrasound transmission memberor waveguide. The distal tip may be chosen from the various examplesbelow, including a blunt tip, a beveled tip, a rounded tip, a pointedtip and may further include nodules or ribs (FIG. 25C) that protrudefrom the surface of the tip to enhance breakup of calcium. Arrows showexemplary patterns of use.

The distal tip of the ultrasonic catheters of the present invention mayalso take the shape of the waveguide tips that are shown and describedin U.S. Pat. No. 5,304,115, the contents of which is expresslyincorporated by reference herein. U.S. Pat. No. 5,989,208 (“Nita”), thecontents of which is expressly incorporated by reference herein,illustrate some additional tips in FIGS. 2-7A that may also be usefulfor decalcifying a valve leaflet.

The ultrasound transmission members of the present invention maycomprise a solid tube that is coupled to an enlarged distal working end.A central lumen may extend throughout the ultrasonic transmission memberand may be used for aspiration, suction, and/or to receive a guidewire.In the embodiment illustrated in FIGS. 26, 27 and 28, the enlargedworking end 110 (which has a larger diameter than the elongate proximalportion), may comprise a cylindrical portion that comprises a pluralityof elongated members 112. In the illustrated configuration, theelongated members are arranged in castellated pattern (e.g., a circularpattern in which each of the elongated members extend distally) andprovide an opening along the longitudinal axis of the ultrasoundtransmission member. While the elongated members are cylindricallyshaped, in other embodiments, the elongated members may be rounded,sharpened, or the like.

In a further embodiment of the distal working end, similar to theembodiment illustrated above, a central lumen may extend through theultrasound transmission element and through the enlarged distal workingend. In the configuration illustrated in FIGS. 29, 30 and 31, the distalworking end 120 is enlarged and rounded.

In alternative embodiments, the portion of the ultrasound transmissionelement (or waveguide) that is adjacent the distal working end may bemodified to amplify the delivery of the ultrasonic waves from theworking end. The waveguide may comprises a plurality of axial slots inthe tubing that act to create a plurality of “thin wires” from thetubing, which will cause the ultrasonic waves to move radially, ratherthan axially. The enlarged distal working end may then be attached tothe plurality of thin wires. Two embodiments of such a configuration areillustrated in FIGS. 32 and 33. In an alternative embodiment, eachcastellation may be housed on its own shaft extending back to theproximal end of the device. Other potential tip geometries are depictedbelow.

The ultrasonic catheters of the present invention may be adapted toimpart motion to the distal tip that is oscillatory, dottering,circular, lateral or any combination thereof. For any of such distaltips described herein, Applicants have found that the use of a smalldistal tip relative to the inner diameter of the catheter body providesa better amplitude of motion and may provide improved decalcification.In addition, an ultrasonic tip of the present invention can be operatedin a variety of treatment patterns, depending on the region of theleaflet or annulus that is being treated, among other things. Forexample, the treatment pattern, either controlled by the user programmedinto the treatment device, may be a circular motion to provide rings ofdecalcification on the surface being treated, a cross-hatching patternto break up larger deposits of calcium (FIG. 24), or a hemispherical(FIG. 36) or wedge-shaped (FIG. 37) pattern when one leaflet or regionis treated at a time. It is within the scope of the present invention touse combinations of any of the patterns listed, or to employ more randompatterns, or simply a linear motion.

Certain safety mechanisms may be incorporated on the treatment catheterand related components to ensure that the treatment device does notperforate or otherwise degrade the leaflet. In one embodiment, a forcelimiting feature may be incorporated into the treatment catheter shaftas shown in FIG. 38, where a structure 140 can contract in response toforce applied to catheter 142 in the direction of arrows 144.

In another embodiment, features of the catheter shaft may limit theforce that is delivered to the tissues. A soft distal tip 150 (FIG. 39)on a relatively rigid catheter shaft 152, where the forces can deflectthe tip, as shown in FIG. 40.

In addition, the treatment catheter 200 may be advanced through a sheath202 that acts as a depth limiter to the treatment catheter as shown inFIGS. 41 and 42. These various safety features may be incorporated intoany of the treatment devices of the present invention, regardless of theenergy employed.

An assembly of an ultrasonic catheter of the present invention is shownin FIG. 43, including an ultrasonic transmission member 210, atransmission-head 212, a guide wire GW, a suction cup 214, a spring 216,and catheter body 218.

Another embodiment of an ultrasonic catheter 220 includes a PZT stack222 and a distal horn 224 at the distal end of the device as shown inFIG. 44

The advantage of the embodiment of FIG. 44 that it eliminates a longwaveguide and the losses that occur when using a long waveguide. In thisembodiment the suction housing would fit over the PZT stack and theultrasonic horn. Certain useful ultrasound elements are depicted in U.S.Pat. No. 5,725,494 to Brisken, U.S. Pat. No. 5,069,664 to Zalesky, U.S.Pat. No. 5,269,291 and U.S. Pat. No. 5,318,014 to Carter, the contentsof which are expressly incorporated by reference in their entirety.

The proximal end of the ultrasonic catheter of the present invention maybe configured according to the schematic depicted in FIG. 45. Knobs 230on a proximal housing 232 are coupled to control wires that areconnected to the distal end of the device. These knobs operate totension the control wires thereby manipulating the angle of the distalend. Controls 234 for the steerable guide, such as gearing, pins, andshafts, are housed in the control box 236 on which the knobs arelocated. The main body of the treatment device further comprises anouter shaft and an inner shaft connected to slide knob. In turn theinner shaft is operatively connected at the distal end of the device tothe housing such that when the slide knob is retracted the housing istranslated from a retracted position to an extended position, or viceversa. Further depicted in FIG. 45 is a drive shaft or drive coil 230that is operatively connected to an energy source or prime mover, forimparting motion to the drive coil. Drive coil terminates in the distalend of the device at the working element that contacts the tissue to betreated. Alternatively, in designs utilizing ultrasound, the ultrasonicwaveguide or transmission element may be positioned within the outershaft and/or inner shaft.

Mechanical Treatment Catheter and Methods

In addition to ultrasound treatment catheters described above, thepresent invention further provides treatment catheters and methods thatuse mechanically activatable tips to mechanically disrupt or obliteratethe calcium on the leaflets. In general, the catheters will comprise acatheter body that comprises one or more lumens. A drive shaft (orsimilar element) may extend from a proximal end of one of the lumens tothe distal end of the lumen. A distal working element may be coupled to(or formed integrally from) the drive shaft and will be configured toextend at least partially beyond a distal end of the catheter body. Theproximal end of the drive shaft may be coupled to a source of mechanicalmotion (rotation, oscillation, and/or axial movement) to drive the driveshaft and distal working element.

The catheters of the present invention may use a variety ofconfigurations to decalcify the leaflet. Some examples of the workingelements and distal ends of the catheter body that may be used aredescribed below.

In one embodiment (FIG. 46), the distal end of the catheter 240comprises a suction housing 242 that may be used to contact and/orisolate the leaflet that is being decalcified. While the suction housingis illustrated as a funnel shaped element, in alternative embodiments,the suction housing may be of a similar shape as the leaflets that areto be treated (as described above). The suction housing 242 may befixedly coupled to the distal end of the catheter body 240 or it may bemovably coupled to the distal end portion. In such movable embodiments,the suction housing may be moved from a retracted position (not shown),in which the suction housing is at least partially disposed within thelumen of the catheter body, to an expanded configuration (shown below).Alternatively, a mechanical clip, clamp or other fixation element may beused to localize the treatment device at the annulus or leaflet to betreated such as that depicted below, including an element placed fromthe retrograde direction and the antegrade direction to secure theleaflets.

In the configuration of FIG. 47, the distal working element may comprisea rotatable, eccentrically loaded coil 250. The distal portion of thecoil may taper in the distal direction and may comprise a ball 252 (orother shaped element) at or near its distal end. Optionally, one or moreweighted elements (not shown) may be coupled along various portions ofthe coil to change the dynamics of the vibration of the coil. As can beappreciated, if the weight is positioned off of a longitudinal axis ofthe coil, the rotation profile of the coil will change. Consequently,strategic placement of the one or more weights could change thevibration of the coil from a simple rotation, to a coil that also has anaxial vibration component.

In another embodiment (FIG. 48), the working element may comprise aneccentrically loaded non-tapering coil 260. The coil may or may notcomprise a ball or weight at its distal tip.

In yet another embodiment (FIG. 49), the distal coil may comprise anelongated distal wire tip 270 in which at least a portion extendsradially beyond an outer diameter of the distal coil working element. Asillustrated, the distal wire tip may comprise one (or more) balls orweights. The distal wire tip may be curved, straight or a combinationthereof. As an alternative to (or in addition to) the aforementioneddistal coils, the distal working element may comprise a “drill bit” typeimpeller or a Dremel type oscillating or rotating member at the distaltip that is configured to contact the calcification and mechanicallyremove the calcification from the leaflet. As can be appreciated, suchembodiments will be rotated and oscillated in a non-ultrasonic range ofoperation, and typically about 10 Hz to 20,000 Hz, preferably 100 Hz to1000 Hz. In such configurations, rotation of the shaped impellers willtypically cause the calcification debris to be moved proximally towardthe lumen in the catheter body. In some configurations, the impeller maycomprise rounded edges so as to provide some protection to the leaflets.In each of the above mentioned embodiments, a sheath may cover therotating elements to provide protection or to provide more directedforce by transmitting the rotational and axial movements through thesheath.

The working elements may also comprise mechanically rotating devices. Inthe embodiment of FIG. 50, an oval shaped burr 280 is shown that theorientation of which ranges from vertically aligned with the centralaxis of the device (rotating axis) to 90 degrees or more from thecentral axis of the device. This off axis orientation allows a range ofdebridement locations and may be more applicable for certain situations,such as stenoses that are located eccentrically within the valveannulus, or to treat leaflet surfaces that are angled with respect tothe central axis of the device. Angulation of the treatment tip relativeto the central axis of the treatment device facilitates fragmentation ofthe calcification by providing increased velocity at the tip region. Asimilar arrangement is shown in FIG. 51, but with a different shaped,more elongate burr 282. In addition, FIG. 52 shows a burr element 284 inthe form of a disk having holes in the face of the disk to allowevacuation of debris through the burr element. It is within the scope ofthe present invention that any mechanical working elements may have aroughened surface, a carbide tip material, or diamond coating to enhancefragmentation of the targeted material. Representative burr elements aremanufactured by several companies such as Ditec Manufacturing(Carpenteria, Calif.), Diamond Tool (Providence, R.I.), and CarbideGrinding Co. (Waukesha, Wis.).

In alternative methods, it may be possible to position an impellerelement 290 (FIG. 53) proximal to the aortic valve and not actuallycontact the leaflets. The rotation of the impeller may cause a vortex toremove calcific material off of the leaflet and into the suction housingand catheter body. The impeller may take a variety of forms such as theone described in U.S. Pat. No. 4,747,821 to Kensey, the contents ofwhich are expressly incorporated herein by reference.

In another configuration, a rotating grinder head 292 (FIG. 54) may becoupled to the distal coil 294. The rotating grinder distal tip can takea variety of shapes. In the configuration illustrated below, the grinderdistal tip is convex shaped and comprises a plurality of holes that arein a radial circular pattern around a central opening that is incommunication with an axial lumen of the drive shaft. In such aconfiguration, the grinder distal tip is symmetrically positioned aboutthe longitudinal axis of the distal coil and the rest of the driveshaft. The radial openings allow for irrigation and aspiration ofparticles. In some configurations, the grinder distal tip may compriseabrasive material, such as diamond dust, to assist in removal of thecalcific material from the aortic valve.

In another grinder distal tip configuration shown in FIGS. 55 and 56,the grinder distal tip may comprise a flat pate 300. The flat grinderdistal tip may comprise an abrasive material, holes, and/or machinedprotrusions or nubs. Such elements may be used to enhance thecalcification removal from the leaflet.

In an alternative configuration as shown in FIG. 57, a grinder distaltip 304 may be mounted eccentrically about the distal coil 306 so thatupon rotation, the grinder tips may cover a greater surface area of theleaflet without having to enlarge the size of the grinder distal tip.The figure below illustrates the flat grinder distal tip, but it shouldbe appreciated that any of the distal tips described herein may bemounted eccentrically with the distal coil.

In another embodiment, the distal working element may comprise acastellated mechanical tip, such as that shown above for the ultrasonicworking element. Optionally, the castellated tip may have an impellerthat is set back from the distal tip.

In yet another embodiment, the present invention may use the Rotablatordevice that is described in U.S. Pat. No. 5,314,407 or 6,818,001, thecomplete disclosure of which are expressly incorporated herein byreference, to decalcify a leaflet. The Rotablator (as shown below) maybe used as originally described, or the distal tip may be modified byflattening the tip, applying diamond dust on the tip, making the distaltip more bulbous, or the like. See FIG. 58 which is taken from the '407patent.

The air turbine used for the Rotablator may be used to power some or allof the aforementioned mechanically-based treatment catheters. The airturbine provides an appropriate amount of torque and speed fordisruption of calcium on the leaflets. The torque and speed, combinedwith a low moment of inertia of the drive shaft and distal tips of thepresent invention, reduce the risk of catastrophic drive shaft failure.For example, when the distal tip becomes “loaded” due to contact withthe calcific deposits, the speed of rotation will reduce to zero withoutsnapping or wrapping up the drive shaft. As an alternative to the airturbine, it may also be possible to use a motor with an electronicfeedback system that can sense torque and speeds such that the motor maybe slowed down at appropriate times.

Some embodiments of the treatment catheter may comprise an optionalsheath that surrounds the distal working element. As illustrated in FIG.59, the sheath may comprise a spherical shaped distal tip 310 thatsurrounds the distal working element. An elongated proximal portion isattached to the spherical distal tip and is sized and shaped to coversome or all of the drive shaft that is within the lumen of the catheterbody. The spherical shaped distal tip may comprise an opening 312 thatwill allow for the delivery of a media (e.g., contrast media, coolant,etc.) and/or for passageway of a guidewire. The mechanical element orultrasonic transmission element may extend beyond the tip of the sheath.A similar depiction is shown in U.S. Pat. No. 6,843,797 to Nash, thecontents of which are expressly incorporated herein by reference.

In some embodiments, the sheath may comprise bellows or a flexibleportion that allows for the end of the sheath to bend, extend, and/orretract. The sheath will typically not rotate, and the sheath willtypically be sized to allow the distal working element and the driveshaft to rotate within the sheath. Rotation of the distal workingelement within the sheath will articulate the sheath (which will dependon the shape and type of actuation of the drive shaft) and may create a“scrubbing effect” on the calcific deposits. Advantageously, the sheathwill transmit the mechanical motion of the drive shaft, while providinga layer of protection to the leaflets by controlling the oscillation ofthe working element. The sheath may be made of a variety of materials asknown in the art and reinforced in such a way as to withstand thefriction from the rotation of the distal working element within thespherical distal tip Consequently, one useful material for the sheath issteel, or a braided or other catheter reinforcement technique.

In any of the mechanical embodiments, it may be desirable to circulateor inject a cooling fluid may be to decrease the heat energy seen by thetissue, and assist in the removal of debris during debridement. Such afluid may also assist with tissue fragmentation by providing acavitation effect in either the ultrasonic embodiments or the mechanicalembodiments.

Virtual Decalcification Use of Microspheres and/or Microbubbles

As noted above, most embodiments of the ultrasound treatment cathetersand the mechanical treatment catheters comprise a lumen that runsthrough the catheter body to the distal end. It may be useful to delivera media, such as a cooling fluid, an ultrasound contrast fluid, or thelike, through the lumen to the target leaflet to amplify the effect ofthe energy delivery to the embedded calcific nodules on the leaflet. Inone preferred configuration, the media may comprise microspheres ormicrobubbles. One useful contrast media that may be used with themethods and treatment catheters of the present invention is the Optison™contrast agent (GE Healthcare). Various depictions of techniquesutilizing cavitation and/or microbubbles to enhance a therapeutic effectmay be found in U.S. Pat. RE036939 to Tachibana, and U.S. Pat. No.6,321,109 to Ben-Haim, the contents of which are expressly incorporatedby reference herein in their entirety.

Delivery of the ultrasonic wave through the contrast media that containsthe microbubbles can increase the amount of cavitation or fragmentationenergy delivered to the leaflet. Applying suction during the procedurecan also enhance the fragmentation energy as described by Cimino andBond, “Physics of Ultrasonic Surgery using Tissue Fragmentation: Part Iand Part II”, Ultrasound in Medicine and Biology, Vol. 22, No. 1, pp.89-100, and pp. 101-117, 1996. It has been described that theinteraction of gas bodies (e.g., microbubbles) with ultrasound pulsesenhances non-thermal perturbation (e.g., cavitation-related mechanicalphenomena). Thus, using a controlled amount of contrast agent withmicrobubbles may enhance the removal of the calcification from theleaflets. A more complete description of the use of microbubbles withultrasound energy is described in Guzman et al., “Bioeffects Caused byChanges in Acoustic Cavitation Bubble Density and Cell Concentration: AUnified Explanation Based on Cell-to-Bubble Ratio and Blast Radius,”Ultrasound in Med. & Biol., Vol. 29, No. 8, pp. 1211-1222, 2003 andMiller et al., “Lysis and Sonoporation of Epidermoid and PhagocyticMonolayer Cells by Diagnostic Ultrasound Activation of Contrast AgentGas Bodies,” Ultrasound in Med. & Biol., Vol. 27, No. 8, pp 1107-1113,2001, the complete disclosures of which are incorporated herein byreference.

It should be appreciated however, that the use of microbubbles are notlimited to the ultrasound or mechanical treatment catheters. Forexample, as shown below, the contrast media may be used with an RFcatheter or a piezoelectric-based catheter. In the RF catheterembodiment, the catheter body may comprise two RF electrodes positionedat or near the distal end of the catheter. The media with themicrobubbles may be delivered to the target leaflet through the lumen ofthe catheter, and an RF energy may be delivered between two leads todeliver energy to the microbubbles. In some embodiments, it may bedesirable to deliver RF energy to the calcification on the leafletswithout the use of the microbubbles. In other embodiments, it may bedesirable to use other types of energy sources to deliver energy to theleaflets.

As an alternative to RF electrodes, it may be possible to position apiezo film 330 at the distal tip of the catheter (FIG. 60). Wire leadswill extend through, within (or outside) the lumen of the catheter bodyand will be coupled to a generator. If the wire leads are disposedwithin the lumen of the catheter body, the catheter may comprise aninner tube to insulate the wires. The media may be delivered through theinner lumen of the catheter body and exposed to the piezo film at thedistal end of the catheter body, and the energy may be delivered fromthe piezo film and into the media with the microbubbles.

Protection

In a further aspect of the present invention, protection devices andmethods may be used to trap and evacuate debris from the treatment site.In one embodiment shown in FIGS. 61 and 62, a filter device 336 islocated on the shaft of a guide catheter 338. This structure may alsoprovide anchoring of the guide catheter in the aortic root to provide astable access system to the valve or placing additional treatmentcatheters.

In another embodiment (FIG. 63), a filter device is deployed to protectthe entire region of treatment and may include a systemic filteringdevice 340 such as those where blood and aspirate are removed from thearterial side of the vasculature, filtered and then infused back intothe venous circulation, further details in U.S. Pat. No. 6,423,032 toParodi, the disclosure of which is expressly incorporated herein byreference. A suction port 342 surrounds the ultrasound probe 344 at thedistal end of catheter 346.

It may be advantageous to have filtering applied more locally closer tothe treatment site (e.g. one leaflet at a time), to protect localstructures such as the ostium of the coronaries located just above theaortic valve. Such a filtering device may be used in conjunction withtreatment devices, such as the ultrasonic suction catheter shown in FIG.64, where filter device 350 covers a single leaflet which is alsoengaged by ultrasonic probe 352 at suction port 354. Further, the filtershape may be optimized to access the most relevant leaflet or treatmentsite, as shown in FIG. 6. Any of the above filtering or protectionsystems may be used with any of the treatment catheters disclosedherein.

Numerous features of the present invention aid in directing, positioningand stabilizing the treatment catheter optimally at the site of thedisease to be treated. In addition to catheter and guide features,baskets, anchor or filter configurations that seat within the valve,certain methods may be used to position the catheter. For example, theheart may be connected to a pacing lead and the heart then paced at anincreased rate, for example 200 beats per minute, which then holds theaortic leaflets in a relatively fixed location arresting blood flow andallowing the treatment catheter of the present invention to be appliedto at least one leaflet. Following placement of the catheter, such as asuction housing, pacing is stopped, and the remaining leaflets notengaged by the catheter, function normally. In the event that allleaflets are engaged at once, it may be necessary to provide flowthrough the treatment catheter, such as in a perfusion balloon or deviceknown in the art, some features of which are shown in U.S. Pat. No.4,909,252 to Goldberg the disclosure of which is expressly incorporateby reference herein.

Imaging

Features of the present invention include various devices and methodsfor monitoring and imaging prior to, during and post procedure. Variousimaging modalities may be employed for this purpose, includingintracardiac echocardiography (ICE), transesophageal echocardiography(TEE), fluoroscopy, intravascular ultrasound (IVUS), angioscopy,infrared, capacitive ultrasonic transducers (cMUTs) available fromSensant, Inc./Seimens (San Leandro, Calif.) or other means known in theart. For example the treatment catheter may have an imaging deviceintegrated into the housing or treatment element catheter shaft, such asa phased array intravascular ultrasound element. In some embodiments itmay be advantageous to construct the device of the present invention sothat they working element is a separate, removable element that iscoaxial with the sheath to enable the operator to remove the workingelement and place an imaging element in its place.

Imaging may become critical at various stages of the procedure,including diagnosing the type and location of the disease, placing thetreatment catheter, assessing the treatment process, and verifying thefunction of the valve once it is treated. Imaging devices may be placedlocally at the treatment site, such as on the catheter tip, or catheterbody, alongside the treatment catheter, or in more remote locations suchas known in the art (e.g. superior vena cava, esophagus, or rightatrium). If the imaging element is placed on the treatment catheter, itmay be adapted to be “forward looking” e.g. image in a plane or multipleplanes in front of the treatment device.

It is also within the scope of the present invention to employinterrogation techniques or other imaging modalities, such as infraredimaging to see through blood for direct visualization of the treatmentsite, or elastography, the ultrasonic measurement of tissue motion, tosense what type of tissue is targeted, e.g. leaflet tissue or calcium,or to sense the region of the valve that is most calcified. Elastographyin this context may be performed using an intravascular ultrasound(IVUS) catheter, either a mechanical transducer or phased array system,such as those described in “Characterization of plaque components andvulnerability with intravascular ultrasound elastography” Phys. Med.Biol. 45 (2000) 1465-1475, the contents of which is expresslyincorporated by reference herein. In practice, the transducer may beadvanced to a treatment site on the valve, and using either externallyapplied force, or “periodic excitation” of the tissue region either byexternally applied force or the naturally occurring movement in thetissue itself (such as the opening and closing of the valve leaflets),an initial baseline reading can be taken. This baseline could be set byengaging the region or leaflet to be treated with a suction catheter ofthe present invention (including circulating fluid within the treatmentsite), inserting an ultrasound transducer through the treatment catheterup to the treatment site, and interrogating the targeted region with theultrasound transducer to establish the elasticity of the region(stress/strain profile). For a particular region of the leaflet,infusion can then be stopped, putting the leaflet under additionalstress (by suction alone) and the displacement in the stress/strainprofile can be noted and evaluated to direct the treatment device tothose locations showing less elasticity (“stiffer” regions indicatingthe presence of calcific deposits. See also those techniques set forthin “Elastography—the movement begins” Phys. Med. Biol. 45 (2000)1409-1421 and “Selected Methods for Imaging Elastic Properties ofBiological Tissues” Annu. Rev. Biomed. Eng. (2003) 5:57-78, the contentsof which are expressly incorporated by reference herein.

In some instances, for example with ultrasound or laser, the sametransducer or fiber optic that is used to interrogate or image theregion may also be used to break up or treat the underlying calcificdeposits. Certain parameters may be adjusted to transition the therapydevice from diagnostic to therapeutic, including frequency, power, totalenergy delivered, etc.

In addition, other characterization techniques may be employed to bothtarget the calcific region to be treated or assess the result of atreatment, including MRI, Doppler, and techniques that utilizeresistivity data, impedance/inductance feedback and the like. Usingimaging and other monitoring techniques such as those described, canresult in a more targeted procedure that focuses on removing calcificdeposits and limits potential tissue damage to the leaflet and annulusthat can lead to an unwanted proliferative response.

Energy Sources/Methods of Treatment

A variety of energy modalities may be used in the treatment cathetersenvisioned by the present invention. Those modalities more specificallyuseful for breaking down or obliterating calcific deposits may beultrasonic energy, laser energy and the like. Specifically, some Er:YAGlasers may specifically target calcium when operated in appropriateranges. Some detail of targeted bone ablation supports this as found in“Scanning electron microscopy and Fourier transformed infraredspectroscopy analysis of bone removal using Er:YAG and CO₂ lasers” JPeriodontol. 2002 June; 73(6):643-52, the contents of which areexpressly incorporated by reference herein. Alternatively, energy may bedelivered to selectively remove tissue from around or over a calciumdeposit by employing a resurfacing laser that selectively targetswater-containing tissue resulting in controlled tissue vaporization,such as a high-energy pulsed or scanned carbon dioxide laser, ashort-pulsed Er:YAG, and modulated (short-and-long-pulsed) Er:YAGsystem. This application of energy may be useful for accessing plaque orcalcium that is distributed between the leaflets (spongiosa). Inpractice, it would be desirable to remove the layer of tissue coveringthe deposit so that the majority of the leaflet remained intact andshielded from unnecessary thermal damage. Further, such specific tissuedestruction may also be applied to the removal of scar tissue or regionsof hypertrophy within the valve annulus as part of the treatment of thepresent invention.

The ultrasonic treatment catheters of the present invention may beoperated in ranges between 5 and 100 kHz, for example 10-50 kHz, with anoscillation rate in the range of 10-200 microns, for example 75-150microns (maximum travel between 20-400 microns). In addition, tominimize potential for thermal damage or other tissue damage, it may beadvantageous to operate the treatment devices in a pulsed manner, suchas a 5-50% duty cycle, for example a 5-20% duty cycle, and to minimizethe tissue that is exposed to the energy application by carefullytargeting the delivery of energy to the most diseased regions.

In addition, it may be advantageous to focus the treatment on certainlocations of the diseased valve where removing or reducing calciumdeposits result in the greatest amount of restored leaflet mobility andresulting valve function. For example, deposits within the annulus ofthe valve, at the nadir of the leaflet, in the mid-section of theleaflet, or at the commissures may be initially targeted. A schematicdepiction of these various positions with the valve are depicted inFIGS. 66, 67, and 68, where FIGS. 67 and 68 are cross-sections alonglines A-A and B-B of FIG. 66, respectively.

Depending on the type and frequency of energy used, the treatmentcatheters of the present invention may also be utilized to not onlyremove calcium, but also to remove or obliterate the leaflet itself,such as in preparation for implantation of a minimally invasiveprosthetic valve, such as those disclosed in U.S. Pat. No. 5,840,081 andU.S. Pat. No. 6,582,462 to Anderson, US Patent Application 2004/0092858to Wilson, PCT Publication WO 2004/093728 to Khairkhahan, WO 2005/009285to Hermann and the like, the disclosures of which are expresslyincorporated herein by reference. Pre-treatment with devices of thepresent invention may facilitate placement of such prosthetic valvessince removing calcium from the site of implantation may reduceperivalvular leak, dislodgement, and may result in a larger prosthesisbeing implanted due to an increased effective valve orifice.

Implantable Devices

A. As an alternative or adjunct to the devices described above which areremoved once the repair is achieved, devices may be provided which aretemporarily or permanently implanted across or within the aortic valve.The devices which appear below are all intended to remain for at least aperiod of time within the body after the repair of the stenosis has beencompleted in order to prevent or delay the valves from degenerating, byeither recalcifying, fusion of leaflets, and restenosing. An implant ofthe present invention is depicted in FIG. 67 in either a sub annular 360or supra annular position 362.

In some embodiments, it may be desirable to place an implant such as thecoil depicted below, to extend both sub annular and supra annular toprovide additional support to the valve and provide a greater treatmentarea across the valve. The coil design of this embodiment has a singlestrut that joins the two ring portions but is low profile enough that isdoes not occlude the coronaries just above the valve annulus. See, FIG.68. Because of its open structure, the supra annular portion of theimplant can extend above the coronaries into the aortic root foradditional anchoring. See, FIG. 69.

In a further embodiment, the implant may be formed of a wire, series ofwire, or cellular structure similar to that used in peripheral orcoronary stents. To better seat in the valve annulus, or below thevalve, it may be advantageous to form the implant ring to follow thecusps of the valve, in a sinusoidal form. In addition, the implant ringmay have struts that extend to seat against the annulus of the valve toprovide structure or further disseminate a pharmacologic coating atspecific valve sites. See, FIGS. 70, 71, and 72.

In yet another embodiment, the implant may be formed of multiple loops,such as three loops 120 degrees from each other. See, FIGS. 73-76.

In this embodiment, and others depicting wire forms, the wire may have adiameter between 0.020″ and 0.250″ depending on the force desired. Inaddition, the wire may be flat and the structure may include a meshbetween the loops to provide a larger surface area for supporting thevalve or delivery the pharmacologic agent. The loops of this device maybe moved distally and proximally in a cyclic way to further open thevalve leaflets and disrupt plaque as a stand alone therapy. The devicemay then be permanently implanted as detailed above. It may be desirableto recapture the device, either once the valve has been treated, orduring positioning of the permanent implant to ensure proper placement.A recapture device may be the delivery catheter from which the implantis deployed, or may include an expandable funnel on the distal end of aretrieval catheter or may include any number of mechanical devicesincluding a grasper or a hook that mates with a hook on the implant, orgrasps the implant at some point such that it may be drawn into thedelivery sheath and removed from the body.

The structure of any of the implants described herein may have surfaceenhancements or coatings to make them radiopaque or echogenic forpurposes of procedure assessment as is known in the art. As is furtherknown in the art in the field of coronary artery stenting, the devicesdescribed may be permanent, removable, or bio-erodable. They canincorporate anti-restenosis agents or materials such as those set forthabove, in the form of coatings, holes, depots, pores or surfaceirregularities designed into or applied onto the devices. In addition,the implants can be formed of certain calcification resistant materialssuch as those set forth in U.S. Pat. No. 6,254,635, the contents ofwhich are expressly incorporated by reference herein. Further, implantsof the present invention may be configured to emit a slight electricalcharge. Since calcium is positively charged, it may be advantageous torepel calcium by positively charging the surface of the aortic implant.In addition, electrical energy may be supplied by the implant tominimize calcification by an implantable pacemaker type device asdescribed in U.S. Pat. No. 6,505,080, which is expressly incorporated byreference herein.

Further, it is within the scope of the present invention to combinecertain mechanical procedures and implants with various appropriatepharmacologic agents such as those listed previously. Anti-restenosisagents which may be useful in this application may be chosen from any ofthe families of agents or energy modalities known in the art. Forexample, pharmaceutical agents or their analogues such as rapamycin,paclitaxel, sirolimus or nitric-oxide enhancing agents may be coatedonto these devices using drug eluting coatings, incorporated intointentionally created surface irregularities or specific surfacefeatures such as holes or divots. The devices may be designed for druginfusion through the incorporation of coatings or other surfaces toadhere the agents to the implants utilized to perform the procedures ofthe present invention, or may be prescribed for oral administrationfollowing procedures of the present invention. For example, following atreatment of the present invention, a patient may be prescribed a doseof statins, ACE inhibitors or other drugs to prolong the valve functionprovided by the intervention.

FIGS. 77-89 represent various embodiments of systems intended for acuteor sub-chronic procedures. These devices may be placed across the aorticvalve and expanded to reopen the aortic valve, and then left in placefor a period of time in order to expose the treated valve toanti-restenosis agents or energy modalities designed to facilitate therepair and/or to prevent restenosis. The device shown in FIGS. 77 and 78features mechanical vanes 400 which extend outward to engage andseparate the fused leaflets at the commissures. The vanes may be made ofany suitable metal, plastic or combination. They may be self expanding(made from nitinol or elgiloy, for instance) or they might bemechanically actuated using a pneumatic, hydraulic, threaded or othermechanical actuation system. The vanes might be deformable members asshown above, or each vane might be made up of several more rigid partsconnected at hinged portions to allow expansion and contraction of theunit. The vanes may be designed with a cross section which isrectangular in shape, with the narrower edge designed to facilitateseparation of fused leaflets and to fit within the commissures withoutimpacting the ability if he valves to close. The wider face of theserectangular vanes would contact the newly separated edges of theleaflets. As an alternative to the rectangular cross section, the vanesmight be designed to have more of a wing-shaped or other cross sectionalshape to minimize turbulence within the bloodstream and to minimizetrauma to the valve leaflets.

The device of FIGS. 79 and 80 shows a balloon system to be used inaccordance with the inventive methods. The balloon 410 may feature aplurality of holes 412 to be used for the infusion of anti-restenosisagents as described in more detail below. These holes may be smallenough to allow only a slight weeping of the agents to be infused, orthey might be of a size which would allow more rapid infusion or agreater volume of infusate to be delivered. The holes might be placed ineven distribution around the circumference of the balloon, or they mightbe placed to align more directly with the location of the commissures.

The device of FIGS. 81 and 82 comprise a balloon system which combinesfeatures of FIGS. 77 and 78 with those of 79 and 80. Several balloonsare placed such that each balloon aligns with a commissure 424.Inflation of this device may allow continued perfusion of blood out ofthe heart and into the body which the device is in place. This in turnmight low for more prolonged delivery of anti-restenosis agents. Holesmight be placed on the balloons of FIG. 3 similar to the description forthe holes on the device in FIGS. 79 and 80.

Anti-restenosis agents which may be useful in this application may bechosen from any of the families of agents or energy modalities known inthe art. For example, pharmaceutical agents or their analogues such asrapamycin, paclitaxel, sirolimus or nitric-oxide enhancing agents may becoated onto any of the inventive devices using drug eluting coatings,incorporated into intentionally created surface irregularities orspecific surface features such as holes or divots. As described, thedevices may be designed for drug infusion through the incorporation ofinfusion channels and infusion holes in the work-performing elements ofthe devices such as the balloons or commissurotomy vanes shown in thedrawings.

Energy delivery may be achieved by several different modalities and fordifferent purposes. Radiofrequency energy can be applied by energizingthe commissurotomy vanes or by using the pores on the balloons toachieve a wet electrode. Microwave, ultrasound, high frequencyultrasound energy or pulsed electric fields (for the purpose of inducingcellular electroporation) might be used by incorporating antennae orelectrodes into the vanes, balloons or catheter shafts that supportthese work performing elements. Cryotherapy can be achieved bycirculating cooling fluids such as phase-change gases or liquid nitrogenthrough the work performing elements. Multiple modalities might beincorporated into a single device for achieving the goal of durableaortic valve repair.

This energy may be used to facilitate the valve repair, for instance bymaking easier the parting of fused leaflets. Alternatively, the energymay be used to delay or prevent restenosis of the treated valve. Oneexample of the use of energy delivery for the prevention of restenosisis the use of pulsed electric fields to induce cellular apoptosis. It isknown in the art that the application of pulses of electricity on theorder of nanosecond duration can alter the intracellular apparatus of acell and induce apoptosis, or programmed cell death, which is known tobe a key aspect of the mechanism of action of the clinically provenanti-restenosis drugs such as paclitaxel or sirolimus.

These agents or energy applications might be administered while thepatient is in the catheterization lab, over the course of minutes tohours. Alternatively, the devices may be designed to allow the patientto return to the hospital floor with the device in place, so that theinfusion of agents or the application of energy could proceed over thecourse of hours or days.

B. As an alternative or adjunct to the devices described above which areremoved once the repair is achieved and administration of theanti-restenosis agents is completed, devices may be provided which aretemporarily or permanently implanted across or within the aortic valve.The devices which appear below are all intended to remain for at least aperiod of time within the body after the repair of the stenosis has beencompleted in order to prevent or delay the valves from readhering to oneanother and restenosing.

The devices described may be permanent, removable, or bio-erodable. Theycan incorporate anti-restenosis agents or materials into coatings,holes, depots, pores or surface irregularities designed into or appliedonto the devices

The struts 430 may be made of any suitable metal, plastic or combinationas shown in FIGS. 83 and 84. They may be self expanding (made fromnitinol or elgiloy, for instance) or they might be mechanically actuatedduring implantation using a pneumatic, hydraulic, threaded or othermechanical actuation system and then locked into their final positionprior to deployment of the device from the delivery system. The strutsmight be deformable members as shown above, or each strut might be madeup of several more rigid parts connected at hinged portions to allowexpansion and contraction of the unit. The struts may be designed with across section which is rectangular in shape, with the narrower edgedesigned to facilitate separation of fused leaflets and to fit withinthe commissures without impacting the ability if he valves to close. Thewider face of these rectangular struts would contact the newly separatededges of the leaflets. As an alternative to the rectangular crosssection, the struts might be designed to have more of a wing-shaped orother cross sectional shape to minimize turbulence within thebloodstream and to minimize trauma to the valve leaflets.

FIGS. 85-89 show alternate designs for the implantable device. It shouldbe noted that any design for the implant which achieves the goals ofproviding long-term anti-restenosis agents or energy modalities to thetreated regions of the repaired leaflets should be considered assubjects of this invention. Anchoring elements which lie against thewall of the aorta and are generally contiguous with the struts (as shownin FIGS. 83 and 84), which join in the center of the aorta beforereforming with the struts (as in FIGS. 85 and 86), or designs in whichthe struts themselves are the anchoring elements (as in FIGS. 87-89) areall embodiments of the subject invention.

The implantable and bio-erodable devices might all featurepharmaceutical agents or their analogues such as rapamycin, paclitaxel,sirolimus or nitric-oxide enhancing agents, which may be coated onto anyof the inventive devices using drug eluting coatings, or incorporatedinto intentionally created surface irregularities or specific surfacefeatures such as holes or divots.

Additional anti-restenosis agents or energy modalities might bedelivered separate from and/or in addition to those agents that areincorporated onto the implant, for instance as a feature of the deliverysystem.

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the spiritand scope of the disclosure and appended claims.

1. A method for treating a cardiac valve having one or more calcificsites, said method comprising: creating an embolic containment regionover a single valve leaflet having a calcific site while the remainingleaflets continue to function; and delivering energy to the calcificsite to disrupt calcifications at said site under conditions expected tocreate emboli which are contained in said containment region, whereincreating the embolic containment region comprises positioning astructure over the region, wherein the structure does not span anassociated blood vessel, wherein positioning the structure comprisesapproximating the structure against the periphery of the single valveleaflet, wherein delivering energy comprises rotating an element withinthe structure to mechanically remove the calcifications withoutdelivering electrical current to the valve leaflet, and wherein thestructure delivers energy to said single valve leaflet only within saidcontainment region.
 2. The method as in claim 1, further comprisingremoving emboli from the containment region.
 3. The method as in claim1, wherein the structure comprises a housing, balloon, basket, orfilter.
 4. The method as in claim 1, further comprising aspiratingemboli from the region around the calcific site.
 5. The method as inclaim 1, wherein the structure is shaped to engage no more than a singlevalve leaflet.
 6. The method as in claim 5, wherein the structure isshaped to engage no more than a single coronary leaflet, non-coronaryleaflet, or center non-coronary leaflet of an aortic valve.
 7. Themethod as in claim 5, wherein the structure is shaped to engage no morethan a single mitral valve leaflet.
 8. The method as in claim 1, whereinsaid containment region and said calcific site are completely enclosedby positioning said structure against said periphery of said singlevalve leaflet.
 9. The method as in claim 1, wherein the element isrotated in a non-ultrasonic range of operation.
 10. The method as inclaim 1, wherein the element is rotated in an axis which ranges from0-90 degrees with respect to a vertical axis of the structure.
 11. Themethod as in claim 1, wherein the element does not contact the valveleaflet and removes the qualifications by creating a vortex.
 12. Themethod as in claim 1, wherein the element is rotated eccentrically. 13.The method as in claim 1, further comprising: stopping or slowingrotating the element when element becomes loaded with the calcification.14. The method as in claim 1, further comprising: injecting a coolingfluid to the valve leaflet while delivering energy.
 15. The method as inclaim 1, further comprising: pacing a heart of the valve leaflet at anincreased rate to hold valve leaflet in a relatively fixed position. 16.The method as in claim 1, wherein the structure comprises a suction cup.17. The method as in claim 16, wherein positioning the structurecomprises moving the suction cup from a retracted position to anexpanded position.
 18. The method as in claim 1, wherein the structureincludes longitudinal stabilizing elements.
 19. The method as in claim18, wherein positioning the structure comprises using the longitudinalstabilizing elements to seat the structure against the valve leaflet.20. The method as in claim 19, wherein the longitudinal stabilizingelements comprise pleats, rings, or hemispherical elements on a suctioncup.